1. Field of the Invention
The present invention relates to nitrogen containing heterocyclic compounds having sodium channel-inhibiting effects, salts thereof and hydrates of the foregoing, to process for producing the same and to the use of the same as medicine.
2. Related Background Art
Compounds with sodium channel-inhibiting effect are known to be useful for treatment of various types of neuralgia (for example, postherpetic neuralgia, diabetic neuralgia, HIV neuralgia, etc.).
As compounds with sodium channel-inhibiting effect there may be mentioned Lidocaine, Carbamazepine, Mexiletine, Amitriptyline and the like, which are already used as neuralgia treatment agents. For example, Lidocaine is used for treatment of postherpetic neuralgia, and Carbamazepine is used for treatment of trigeminal neuralgia.
It has also been reported that Mexiletine and Lidocaine are effective as analgesics (Pain. 83 (1999) 389-400; European Journal of Pain. 2 (1998) 3-14; Pain. 73 (1997) 123-139).
Compounds with sodium channel-inhibiting activity have been reported to also exhibit the following pharmacological activities and therapeutic effects for diseases other than types of neuralgia.
(i) Compounds with sodium channel-inhibiting activity are used for treatment of epilepsy (Pharmacology & Therapeutics 90 (2001) 21-34).
(ii) It has been reported that Carbamazepine, used as an anticonvulsant, is effective for treatment of manic-depressive psychosis (Biological Psychiatry 51 (2002) 253-260).
(iii) It has been reported that Lidocaine and Mexiletine are effective for various symptoms of multiple sclerosis (Journal of Neurological Sciences 162 (1999) 162-168).
(iv) It has been reported that Lidocaine is effective for treatment of premature ejaculation (Andrologia 34 (2002) 356-359).
(v) Somnolence-inducing effects have been reported for Carbamazepine and Oxocarbazepine which are used as anticonvulsants (Epilepsy 46 (2002) 145-155; CNS Drugs 15 (2001) 137-163), suggesting the possibility of the use of sodium channel inhibitors for treatment of insomnia.
(vi) Activity by sodium channel inhibitors in various neuropathic animal models has been reported, suggesting a protective effect against neuropathy in cerebrovascular disease, cranial injuries and spinal injuries (Trends in Pharmacological Sciences 16 (1995) 309-316).
(vii) The efficacy of sodium channel inhibitors in Parkinson's disease model animals has been published at a scientific conference (31st Annual Meeting of Society of Neuroscience 27 (2001) Abstract 199.16).
Low-molecular weight compounds with sodium channel-inhibiting effects have also been reported, such as the following.
Sodium channel-inhibiting compounds represented by the following general formula (I1):
(WO01/53288).
These sodium channel inhibitors, however, exhibit effects on the cardiovascular system and inhibition effect on hepatic drug metabolizing enzymes, and have therefore been less than satisfactory.